The overall goal is to develop the optimal hypertonic resuscitation formulation for pre-hospital treatment of hemorrhage and trauma. Current methods of isotonic fluid resuscitation for prehospital hypovolemia are often inadequate due to inability to deliver required volume. Small volume resuscitation using highly hyperosmotic/hyperoncotic formulations was developed to provide rapid hemodynamic recovery. However, hypertonic saline formulations cause acidosis; may inadequately increase oxygen delivery/consumption; and aggravate internal bleeding. This research proposal utilizes the recent discovery of a specific Na-Cl-Acetate formulation that offers unique physiological benefits which directly address these problems. Preliminary experiments suggest that such a solution better normalizes acid-base balance and greatly augments cardiac output and oxygen delivery. Another benefit is that resuscitation with this solution results in only a modest increase in systolic blood pressure, thereby minimizing internal bleeding. The research plan is to test an Na-Cl-Acetate Dextran solution in clinically relevant animal models of controlled and uncontrolled hemorrhage. Control groups will be resuscitated with 1) the current standard-of-care isotonic lactated Ringer's; 2) hypertonic saline dextran, and 3) no resuscitation. In one series of experiments, conscious, hypovolemic sheep will be used to carefully evaluate the efficacious dose and the effects on oxygen delivery and consumption. In the other series, anesthetized pigs with uncontrolled aortic bleeding will be resuscitated to determine the effects of resuscitation on uncontrolled internal bleeding to model prehospital trauma. This research may lead to significantly better resuscitation regimens that offer improved efficacy and safety compared to currently used solutions.